This project will elucidate the role of Mg2 ion as a modifier of mammalian cardiac muscle contractility by determining the effects that physiological changes in its intracellular concentration have on Ca 2 ion-activated isometric tension generation. Increases in (Mg 2 ion) in "skinned" (sarcolemma removed) skeletal muscle fibers have been shown to significantly 1) decrease tension generation at any given (Ca 2 ion) and 2) decrease the degree of cooperativity in the tension generating system as evidenced by a change in the steepness of the (Ca 2 ion) versus tension relationship. Total (Mg) is similar (in an mM range) in both skeletal and cardiac muscle. A "skinned" cardiac muscle preparation will be utilized which allows measurement of isometric tension generation in small bundles of ventricular cardiac muscle cells whose surface membranes have been mechanically disrupted. Selected skeletal muscles will also be used for comparison. With the sarcolemma functionally removed, the ionic composition of the media bathing the contractile proteins can be specified and controlled. A computer program will be used to solve the complex equilibria of the bathing solutions. Comparison of the (Ca 2 ion) and (Sr 2 ion) versus isometric tension relationships and maximum tensions will be made at several physiological (Mg 2 ion)'s, since this analysis has been successfully employed in characterizing the nature of the Mg 2 ion and Ca 2 ion interaction in skeletal muscle. In vivo studies of cardiac muscle have shown that Mg is accumulated in response to growth producing stimuli and is lost in response to hypoxia. This study will determine the possible effects of such changes in (Mg) on cardiac contractility and, in addition, will provide information about the molecular control mechanisms of cardiac contraction and difference in control between cardiac and skeletal muscle.